Glioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-?-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with ClinicalTrials.gov under the identifier NCT02852655 (https://clinicaltrials.gov/ct2/show/NCT02852655). Overall design: This dataset contains the transcriptomes of recurrent glioblastoma with either neoadjuvant (1 dose) or adjuvant pembrolizumab treatment
Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
Subject
View SamplesIn Arabidposis thaliana, the msh1 recA3 double mutant shows an extensive mitochondrial genome rearrangement and displays pronounced thermotolerance.
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
Specimen part
View SamplesSingle mutant msh1
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
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View SamplesDouble mutant msh1 and recA3
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
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View SamplesThe soybean msh1 RNAi transgenic line show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
MutS HOMOLOG1 is a nucleoid protein that alters mitochondrial and plastid properties and plant response to high light.
Specimen part
View SamplesThe soybean msh1 RNAi transgenic line show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
MutS HOMOLOG1 is a nucleoid protein that alters mitochondrial and plastid properties and plant response to high light.
Specimen part
View SamplesThe Arabidopsis msh1 mutant show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
The chloroplast triggers developmental reprogramming when mutS HOMOLOG1 is suppressed in plants.
Specimen part
View SamplesStem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that DDX6 is necessary for maintaining human epidermal progenitor cell self-renewal.
DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
Specimen part
View SamplesWe used microarrays to investigate gene expression changes in the pancreas of RasGrf1 KO mice. These animals have a reduction in the number and size of the pancreatic islets which lead to lower levels of insulin and glucagon in their blood.
Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells.
Specimen part
View SamplesWe used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death.
Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.
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